A developing area of interest to our laboratory is investigating novel mechanisms of mitochondrial regulation that may be important for cardiovascular function. We have recently shown that the tumor suppressor gene p53 profoundly affects exercise capacity in mice, and we have identified the mediator gene as an assembly factor of the cytochrome c oxidase complex. This finding may offer a molecular explanation for some of our previous observations of p53 dependent oxidant generation and heart failure by chemotherapeutic agents. We are now initiating studies to translate some of these basic observations to human studies.[unreadable] [unreadable] Our laboratory is also molecularly dissecting easily accessible human cells important for atherosclerosis to gain new insights into the disease process. Using unbiased approaches, we have identified monocyte and macrophage transcription factors as a reactive disease markers and mediators of disease. Studies are underway to elucidate the molecular mechanisms of candidate genes in pathogenesis using mouse and human model systems.